Search

Females are relatively resistant to salt-sensitive hypertension than males, but the mechanisms are not completely elucidated. We recently demonstrated a decisive role of macula densa neuronal NOS1β (nitric oxide synthase β)-mediated tubuloglomerular feedback (TGF) in the long-term control of glomerular filtration rate, sodium excretion, and blood pressure. In the present study, we hypothesized that the macula densa NOS1β-mediated TGF mechanism is different between male and female, thereby contributing to the sexual dimorphism of salt-sensitive hypertension. We used microperfusion, micropuncture, clearance of fluorescein isothiocyanate-inulin, and radio telemetry to examine the sex differences in the changes of macula densa NOS1β expression and activity, TGF response, natriuresis, and blood pressure after salt loading in wild-type and macula densa-specific NOS1 knockout mice. In wild-type mice, a high-salt diet induced greater increases in macula densa NOS1β expression and phosphorylation at Ser 1417, greater nitric oxide generation by the macula densa, and more inhibition in TGF response in vitro and in vivo in females than in males. Additionally, the increases of glomerular filtration rate, urine flow rate, and sodium excretion in response to an acute volume expansion were significantly greater in females than in males. The blood pressure responses to angiotensin II plus a high-salt diet were significantly less in females than in males. In contrast, these sex differences in TGF, natriuretic response, and blood pressure were largely diminished in knockout mice. In conclusion, macula densa NOS1β-mediated TGF is a novel and important mechanism for the sex differences in salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

Impaired renal autoregulation permits more transmission of disturbance in systemic blood pressure, which initiates barotrauma in intrarenal microvasculatures such as glomerular and tubulointerstitial capillaries, contributing to the development of kidney damage and deterioration in renal function, especially under the conditions with high blood pressure. Although it has been postulated that autoregulatory efficiency is attenuated in the aging kidney, direct evidence remains lacking. In the present study, we measured the autoregulation of renal blood flow, myogenic response of afferent arteriole (Af-Art), tubuloglomerular feedback in vivo with micropuncture, as well as tubuloglomerular feedback in vitro in isolated perfused juxtaglomerular apparatus in young and aged C57BL/6 mice. We found that renal blood flow was not significantly changed in response to a defined elevation of renal arterial pressure in young mice but significantly increased in aged mice. Additionally, myogenic response of Af-Art measured by microperfusion with a stepwise increase in perfusion pressure was significantly blunted in the aging kidney, which is associated with the attenuation of intraluminal pressure-induced intracellular calcium increases, as well as the reduced expression of integrin α5 (Itga5) in Af-Art. Moreover, both tubuloglomerular feedback in vivo and in vitro were nearly inactive in the aging kidney, which is associated with the significantly reduced expression of adenosine A1 receptor (A1AR) and suppressed vasoconstrictor response to adenosine in Af-Art. In conclusion, this study demonstrates that aging impairs renal autoregulation with blunted myogenic response and inhibited tubuloglomerular feedback response. The underlying mechanisms involve the downregulations of integrin α5 and A1AR in the Af-Art. [ABSTRACT FROM AUTHOR]

Non-O type of ABO blood group has been associated with a predisposition to coronary heart disease. It is thought that this association is partly mediated by increased cholesterol levels in non-O-type individuals. In this study, we sought to estimate the mediation effect size.In a group of individuals (n=6476) undergoing coronary angiography, we detected associations of non-O type with significant coronary artery disease with >50% stenosis in ≥1 coronary arteries (odds ratio, 1.24; 95% confidence interval, 1.10-1.39; P=2.6×10-4) and with prevalent or incident myocardial infarction (odds ratio, 1.22; 95% confidence interval, 1.09-1.37; P=1.2×10-3). Subjects of non-O type had higher levels of total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol (mean [SEM] in mmol/L: 4.931[0.021], 3.041 [0.018], and 3.805 [0.020] in non-O type compared with 4.778 [0.026], 2.906 [0.021], and 3.669 [0.024] in O type; P=3.8×10-7, P=1.5×10-7, and P=3.1×10-7, respectively). Mediation analyses indicated that 10% of the effect of non-O type on coronary artery disease susceptibility was mediated by increased low-density lipoprotein cholesterol level (P=7.8×10-4) and that 11% of the effect of non-O type on myocardial infarction risk was mediated by raised low-density lipoprotein cholesterol level (P=2.0×10-3).In a model in which it is presumed that cholesterol is a mediator of the associations of ABO group with coronary artery disease and myocardial infarction, around 10% of the effect of non-O type on coronary artery disease and myocardial infarction susceptibility was mediated by its influence on low-density lipoprotein cholesterol level. [ABSTRACT FROM AUTHOR]

Background: Transradial coronary catheterization is widely used as a diagnostic or interventional procedure for coronary disease. However, it can lead to adverse complications, such as radial artery occlusion. We sought to determine whether preprocedural injection of nitroglycerin at the radial artery puncture site reduces radial artery occlusion. Methods and Results: A total of 188 patients undergoing transradial coronary catheterization were randomized in a single-blind fashion to receive subcutaneous injection of 0.5 mL 0.1% nitroglycerin or a placebo at the radial artery puncture site. The participants underwent ultrasound examinations of the radial artery before and at 24 hours after the procedure. Of the 188 patients enrolled, 182 completed the study, as the procedure failed in 2 participants in the nitroglycerin-treated group and 4 in the placebo group. Baseline demographic and clinical characteristics were similar between 2 groups. Comparing the radial artery diameters before and after the operation, there was a statistically significant increase in the nitroglycerin-treated group (2.48±0.45 versus 2.45±0.46 mm; P =0.003) but a decrease in the placebo control group (2.41±0.50 versus 2.46±0.49 mm; P <0.001). Importantly, the incidence of radial arterial occlusion was substantially lower in the nitroglycerin-treated group than in the placebo control group (5.4% versus 14.4%; P =0.04). There was not significant difference in other complications (forearm hematoma and radial artery pseudoaneurysm, respectively), and there was no incidence of cause hypotension or an intolerable headache. Conclusions: Subcutaneous injection of nitroglycerin at the radial artery puncture site dilates the radial artery and reduces the incidence of early radial artery occlusion post-catheterization. Clinical Trial Registration: URL: https://www.chictr.org.cn. Unique identifier: ChiCTR-IPR-15006559. [ABSTRACT FROM AUTHOR]

Background: End-stage renal disease (ESRD) is complicated by high blood pressure (BP) and severe atherosclerosis, which may lead to different values of BP measured by invasive and noninvasive methods. However, the differences in BP values between these two methods and their possible mechanisms in ESRD have not been investigated., Methods: Forty-one ESRD patients on dialysis were enrolled in the present study. Invasive BP, noninvasive BP, and carotid hemodynamic variables were obtained through radial artery catheterization, oscillometric methods, and echoarteriography, respectively., Results: We found that noninvasive systolic BP (NISBP) was 30±20 mmHg (P<0.001) lower than invasive systolic BP (INSBP), whereas no significant difference was found in diastolic BP between these two methods. The difference between INSBP and NISBP was correlated with carotid peak systolic velocity (r=0.3550, P=0.0229)., Conclusion: NISBP could not accurately represent INSBP in ESRD patients on dialysis. The lack of dynamic pressure measurement during NISBP measurement may contribute to the difference between NISBP and INSBP.